Without limiting the scope of the invention, its background is described in connection with the antibiotic resistance.
The 21st century is witnessing the evolution and dissemination of unprecedented levels of antimicrobial resistance and new resistance mechanisms. The evolution and dissemination of MDR, XDR, and TDR strains of Mycobacterium tuberculosis (Mtb) and the rise of nontuberculous Mycobacteria, make the development of new agents to treat these conditions crucial. Meropenem/clavulanate has been recently proposed as a potential treatment for Mtb, with the meropenem targeting the essential transpeptidase LdtMt2, and the clavulanic acid acting as a beta-lactamase inhibitor to protect the antibiotic from hydrolytic degradation by the beta-lactamase, BlaC. It is recognized, however, that meropenem is a broad spectrum antibiotic, with extensive antimicrobial activity against numerous strains. Long term administration of meropenem, as would be required in treatment of tuberculosis, would adversely affect the microbiome, and thus structural modifications of the carbapenem scaffold that could improve potency and selectivity for the mycobacterial l,d-transpeptidase would be extremely useful.
What is needed are novel compounds with improved activity, relative to meropenem, against both Mtb and Mycobacterium abscessus (Mabs).